Biliary atresia is the most common and perplexing cause of neonatal cholestasis. This disease of the intrahepatic and extrahepatic bile ducts is characterized by periductular inflammation and fibrosis that is associated with the progressive obliteration of the bile ducts (1, 2). Approximately 80–90% of biliary atresia cases are the perinatal or acquired form (1, 2). The rare embryonic form is associated with multiple congenital abnormalities (1, 2). At the time of diagnosis, surgery (Kasai portoenterostomy) is performed in an attempt to reestablish bile flow. However, over 80% of patients with biliary atresia will require liver transplantation, because of the progressive development of biliary cirrhosis (3). In spite of extensive histopathological analysis of surgical specimens from excised extrahepatic biliary systems of infants undergoing portoenterostomy, the underlying mechanisms regulating the pathogenesis of biliary atresia remain poorly understood.

Theories of the pathogenesis of the disease include abnormalities in bile duct development (4), viral infection (5, 6), ischaemia-related obstruction of the bile ducts (3), environmental toxins (7) and autoimmune-mediated bile duct destruction (6). The current working hypothesis for the pathogenesis of perinatal biliary atresia is based on a two-hit model (8). In this model, the first insult occurs during the perinatal period where a still unknown exogenous factor, such as viral infection, triggers the innate immune system in biliary epithelial cells (2, 9). Subsequently, the initial trigger activates an uncontrollable autoimmune response, which manifests as liver fibrosis, accompanied by the destruction of the extrahepatic and intrahepatic bile ducts (2, 9). The type of virus responsible for the initial activation of the innate immune response remains controversial. However, viral infections by the Reoviridae genus (reovirus and rotavirus) are suspected to be involved (5, 6). This theory is supported by animal models of biliary atresia in which transient infection of newborn mice with rotavirus is sufficient for the mice to develop progressive inflammation and obstruction of the extrahepatic bile duct (6). The role of the innate immune response in this model was